Applications of Fluorine in Medicinal Chemistry

被引：3086

作者：

Gillis, Eric P. ^{[1
]}

Eastman, Kyle J. ^{[1
]}

Hill, Matthew D. ^{[1
]}

Donnelly, David J. ^{[2
]}

Meanwell, Nicholas A. ^{[1
]}

机构：

[1] Bristol Myers Squibb Res & Dev, Dept Discovery Chem, Wallingford, CT 06492 USA

[2] Bristol Myers Squibb Res & Dev, Discovery Chem Platforms, PET Radiochem Synth, Princeton, NJ 08543 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 58卷 / 21期

关键词：

POSITRON-EMISSION-TOMOGRAPHY; PEPTIDASE-IV INHIBITORS; SELECTIVE NONSTEROIDAL INHIBITORS; LATE-STAGE FLUORINATION; PROTEIN KSP INHIBITORS; HEPATITIS-B-VIRUS; CENTER-DOT-X; CONFORMATIONAL-ANALYSIS; HYDROGEN-BOND; C-F;

D O I：

10.1021/acs.jmedchem.5b00258

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

The role of fluorine in drug design and development is expanding rapidly as we learn more about the unique properties associated with this unusual element and how to deploy it with greater sophistication. The judicious introduction of fluorine into a molecule can productively influence conformation, pK(a), intrinsic potency, membrane permeability, metabolic pathways, and pharmacokinetic properties. In addition, F-18 has been established as a useful positron emitting isotope for use with in vivo imaging technology that potentially has extensive application in drug discovery and development, often limited only by convenient synthetic accessibility to labeled compounds. The wide ranging applications of fluorine in drug design are providing a strong stimulus for the development of new synthetic methodologies that allow more facile access to a wide range of fluorinated compounds. In this review, we provide an update on the effects of the strategic incorporation of fluorine in drug molecules and applications in positron emission tomography.

引用

页码：8315 / 8359

页数：45

共 365 条

[1]

Abraham R. J., 1996, J CHEM SOC FARADAY T, V9, P1949

[2]

CONFORMATIONAL-ANALYSIS .22. AN NMR AND THEORETICAL INVESTIGATION OF THE GAUCHE EFFECT IN FLUOROETHANOLS [J].

ABRAHAM, RJ ;

CHAMBERS, EJ ;

THOMAS, WA .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2, 1994, (05) :949-955

[3]

A simplified protocol for the automated production of succinimidyl 4-[18F] fluorobenzoate on an IBA Synthera module [J].

Ackermann, Uwe ;

Yeoh, Shinn Dee ;

Sachinidis, John I. ;

Poniger, Stan S. ;

Scott, Andrew M. ;

Tochon-Danguy, Henri J. .

JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 2011, 54 (9-10) :671-673

[4]

Design and synthesis of orally available MEK inhibitors with potent in vivo antitumor efficacy [J].

Adams, Mark E. ;

Wallace, Michael B. ;

Kanouni, Toufike ;

Scorah, Nicholas ;

O'Connell, Shawn M. ;

Miyake, Hiroshi ;

Shi, Lihong ;

Halkowycz, Petro ;

Zhang, Lilly ;

Dong, Qing .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (07) :2411-2414

[5]

Functionalization of Fluorinated Molecules by Transition-Metal-Mediated C-F Bond Activation To Access Fluorinated Building Blocks [J].

Ahrens, Theresia ;

Kohlmann, Johannes ;

Ahrens, Mike ;

Braun, Thomas .

CHEMICAL REVIEWS, 2015, 115 (02) :931-972

[6]

Stereoelectronic effects and general trends in hyperconjugative acceptor ability of σ bonds [J].

Alabugin, IV ;

Zeidan, TA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002, 124 (12) :3175-3185

[7]

Alauddin MM, 2012, AM J NUCL MED MOLEC, V2, P55

[8]

A Diverse Series of Substituted Benzenesulfonamides as Aldose Reductase Inhibitors with Antioxidant Activity: Design, Synthesis, and in Vitro Activity [J].

Alexiou, Polyxeni ;

Demopoulos, Vassilis J. .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (21) :7756-7766

[9]

Carbon Trifluoromethylation Reactions of Hydrocarbon Derivatives and Heteroarenes [J].

Alonso, Concepcion ;

Martinez de Marigorta, Eduardo ;

Rubiales, Gloria ;

Palacios, Francisco .

CHEMICAL REVIEWS, 2015, 115 (04) :1847-1935

[10]

The pentafluorosulfanyl group in cannabinoid receptor ligands: synthesis and comparison with trifluoromethyl and tert-butyl analogues [J].

Altomonte, Stefano ;

Baillie, Gemma L. ;

Ross, Ruth A. ;

Riley, Jennifer ;

Zanda, Matteo .

RSC ADVANCES, 2014, 4 (39) :20164-20176

← 1 2 3 4 5 6 7 8 9 10 →